Small molecule induction of neural‐like cells from bone marrow‐mesenchymal stem cells

Wang, Ye; He, Wenfeng; Bian, Hetao; Liu, Chuan; Sy, Li

doi:10.1002/jcb.24021

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…The fate of HSCs is regulated by small molecules that promote self-renewal [181][182][183] . Using small molecules, multipotent MSCs can differentiate into various non-hematopoietic cells, such as chondrocytes [134,184] , osteoblasts [185,186] , hepatocytes [187] , cardiomyocytes [188,189] , adipocytes [190,191] and neuronal-like cells [192][193][194] . Additionally, the maintenance of MSCs is associated with the Wnt signaling pathway [195,196] .…”

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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“…Similar to adult NCSCs, MSCs are able to generate osteogenic, adipogenic, and chondrogenic progeny, although their neuronal differentiation potential is a subject of an ongoing scientific debate [63–65]. At least in vitro , MSCs seem to show the ability to differentiate into neuron-like and Schwann cell-like phenotypes [66, 67] (reviewed in [65]). Concerning their morphological and immunocytochemical properties, as well as the expression profile, MSCs show high degree of similarity to fibroblasts, making them nearly indistinguishable in vivo [68–71].…”

Section: Potential Stem Cell/progenitor Populations Within Mcs Andmentioning

confidence: 99%

Origin and Regenerative Potential of Vertebrate Mechanoreceptor-Associated Stem Cells

Widera

Hauser

Kaltschmidt

et al. 2012

Anatomy Research International

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Meissner corpuscles and Merkel cell neurite complexes are highly specialized mechanoreceptors present in the hairy and glabrous skin, as well as in different types of mucosa. Several reports suggest that after injury, such as after nerve crush, freeze injury, or dissection of the nerve, they are able to regenerate, particularly including reinnervation and repopulation of the mechanoreceptors by Schwann cells. However, little is known about mammalian cells responsible for these regenerative processes. Here we review cellular origin of this plasticity in the light of newly described adult neural crest-derived stem cell populations. We also discuss further potential multipotent stem cell populations with the ability to regenerate disrupted innervation and to functionally recover the mechanoreceptors. These capabilities are discussed as in context to cellularly reprogrammed Schwann cells and tissue resident adult mesenchymal stem cells.

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“…Therapeutic strategy using stem or progenitor cells was proposed as a possibility to treat neurodegenerative disorders replacing the injured brain tissues with cell implants. Embryonic stem cells, mesenchymal stem cells, and neural stem or progenitor cells were proposed as cell candidates [ 4 – 7 ]. Among these cells, neural stem or progenitor cells were found promising as they are able to differentiate to neurons if implanted [ 8 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Fluorescence imaging of in vivo miR-124a-induced neurogenesis of neuronal progenitor cells using neuron-specific reporters

Jang

Lee

et al. 2016

EJNMMI Res

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BackgroundFacilitation of the differentiation of the stem cells toward neuronal lineage is crucial for enhancing the differentiation efficacy of grafted stem cells for the possible treatment of neurodegenerative disorders. MicroRNA124a (miR-124a) has been considered as a neuronal lineage regulator, possessing the capability to activate neuronal differentiation. In this study, using a neuronal promoter-based reporter and live-cell fluorescence imaging, we visualized in vitro and in vivo the enhanced neuronal differentiation of neuronal progenitor cells with miR-124a overproduction.MethodsThe neuron specific alpha1 tubulin promoter-driven RFP reporter (pTa1-RFP) was used to trace the miR-124a-induced neuronal differentiation in live cell condition. MiR-124a or miR-scramble in 10 % glucose buffer was mixed with in vivo-jetPEITM and in vivo fluorescence images were obtained daily using Maestro spectral fluorescent imager.ResultsNeurite outgrowth was clearly seen in F11 cells after miR-124a transfection, and immunofluorescence staining showed increase of Tuj1 and NF at 48 hours. When pTa1-RFP-transfected F11 cells were implanted simultaneously with miR-124a into the nude mice, gradually increasing reporter signals and morphological changes indicated neuronal differentiation for 48 hours in live cells in vitro. The miR-124a-treated F11 cells showed higher reporter signals on in vivo fluorescence imaging than miR-scramble-treated cells, which were verified by ex vivo confirmation of Tuj1 and NF expression.ConclusionsThese results indicated that neuronal reporter-based neurogenesis imaging can be used for monitoring miR-124a acting as neuronal activator when miRNA was injected in in vivo PEI-coated form for miRNA-mediated regenerative therapy.

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Small molecule induction of neural‐like cells from bone marrow‐mesenchymal stem cells

Cited by 7 publications

References 33 publications

MicroRNAs as novel regulators of stem cell fate

MicroRNAs as novel regulators of stem cell fate

Origin and Regenerative Potential of Vertebrate Mechanoreceptor-Associated Stem Cells

Fluorescence imaging of in vivo miR-124a-induced neurogenesis of neuronal progenitor cells using neuron-specific reporters

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